When I completed my Project LEAD® training last summer, I never imagined how many research and community advocacy opportunities I would experience in such a condenced period of time.

My first research-related experience happened just a few months after Project LEAD when a few graduates and I received a scholarship from the Alamo Breast Cancer Foundation (ABCF), to attend the annual, world-renowned San Antonio Breast Cancer Research Symposium in Texas. It was an extraordinary week-long event that gathered near 8,000 researchers, oncologists, surgeons and advocates with the purpose of showcasing the latest research discoveries in the fight against breast cancer. It was exciting to understand most of the conversation and to be able to voice our patient advocate perspective with pharmaceutical companies, research labs and leading experts who shared their projects with us. We made great connections with people from all over the world. And upon returning from the conference, I wrote my first research article—more than 2,200 words. My article was edited by Cancer Magazine for future publication in the annual Hot Topics CD presented by ABCF. My topic was based on one of the symposium presentations and talks about the role of genetics and microenvironments in the development of breast cancer tumors.

A few weeks later, I was nominated and became a consumer reviewer for the U.S. Department of Defense (DOD) Breast Cancer Research Program (BCRP). In early 2013, I traveled to Washington, DC, and took part in the collaborative group of scientists and fellow patient advocates who reviewed hundreds of proposals sent by different national and international scholars who were applying for federal grants to partially fund breast cancer research projects. This was certainly a one-of-a-kind experience and I am thrilled that I recently received an invitation to return again.

Also in early 2013, I was invited by a fellow Californian and NBCC mentor to join the board of the Breast Cancer Care Research Foundation (BCCRF), an organization whose mission is to educate and promote clinical research, access to quality care and advocacy for women with breast cancer and their supporters. Soon after, I was invited to collaborate with a group of wonderful researchers as an advocate in a research proposal that focuses on study patients from my same Latino heritage.

More recently, another group of valuable researchers I admire in the University of Southern California (USC) invited me to be part of the advisory committee of patient advocates to prepare and present a proposal that involves the Adolescent and Young Adult (AYA) community at the USC Norris Comprehensive Cancer Center.

In summary, these past few months have been very rewarding and I am looking forward to continue collaborating in all the advisory committees, community organizations and hospitals that I currently support. Project LEAD taught me not just the basics of breast cancer research and its importance in the fight against this disease, but it also taught me how to be the voice for my community in any cancer research proposal that I am involved with, either as a collaborator or as a reviewer.

I am honored to be named by Health and Human Services Secretary Kathleen Sebelius to the National Advisory Council for the Agency for Health Research and Quality (AHRQ). I’m especially excited by the opportunity this platform presents to move us closer to Breast Cancer Deadline 2020®.

The AHRQ National Advisory Council advises the Secretary of Health and Human Services and the AHRQ Director on setting priorities for a national agenda and strategy to enhance health care research, improve outcomes and reduce the cost of health care services–key strategies for achieving the goals of the deadline. The Council’s 21 individual members serve two-year terms and are selected to represent areas of health care research and quality improvement, clinical practice, health plans, providers and purchasers, health care economics, ethics and public policy. Three members represent patient and consumer interests.

So how does someone like me, diagnosed with breast cancer nearly 19 years ago, develop into an advocate ready, willing, and able to sit at this table?

It started when I attended my first NBCC Advocacy Conference in the late 1990’s. Like many of us not too far out from treatment, I had an emerging yet unfocused energy fed by a growing hunger to learn more about breast cancer and a curiosity about NBCC’s brand of advocacy. I was impressed by NBCC’s mission to end breast cancer, and its strategy to include educated advocates in all areas where decisions about breast cancer are made. The phrase “a seat at every grown-ups table” stuck in my head. I was convinced that NBCC was an organization that would shake the world of breast cancer and I wanted to be part of that.

I jumped right in! NBCC’s three Project LEAD® courses: Basic, Clinical Trials and Quality Care, gave me a knowledge base and helped develop critical thinking skills necessary to participate in research proposal review panels and collaborations, clinical trials improvements initiatives and efforts to improve health care access. I became involved in NBCC initiatives including the Guide to Quality Breast Cancer Care and the Quality Care Measures Initiative. On the legislative and policy front, NBCC has given me the opportunity to indulge a personal passion for the legislative (and sometimes political) process. As Massachusetts Field Coordinator I am proud to lead our state advocates to Capitol Hill to visit our Senators and Representatives to promote NBCC’s legislative priorities. And I am grateful for the mentorship offered by outstanding NBCC advocates–a gift I hope to carry forward in my role as Project LEAD mentor and LEAD Quality Care faculty.

I will bring the entirety of these experiences as I take my seat on the ARHQ Advisory Council. But I also approach this new assignment with keen awareness and deep gratitude that I am blessed with healthy years denied many diagnosed with this disease and a sense of responsibility to best use my talents and abilities to meet the task at hand. Most importantly, I will be firmly guided by our shared commitment to achieve Breast Cancer Deadline 2020®.

Each year the National Breast Cancer Coalition’s (NBCC) Board of Directors determines legislative and public policy priorities for the organization. Since its inception, NBCC has chosen priorities that will have a significant impact on breast cancer. The priorities must have a broad focus that can be accomplished through enactment of legislation or by public policy.

In 2010 NBCC set a deadline to end breast cancer by January 1, 2020. Our strategic plan to accomplish this goal focuses on prevention of primary breast cancer and prevention of metastatic breast cancer. Each priority must fit within this strategic plan.

The process to decide these priorities begins with NBCC’s grassroots. In early January, emails requesting suggestions for priorities are sent to Board members, Field Coordinators and the National Action Network. NBCC staff then researches the issues that have been raised by the grassroots. Next the staff prepares background information on each issue put forward. At the two-day Board meeting in January, the Board members and staff discuss each issue in depth. The Board then decides if a particular issue should be a priority for that year. The Board reviews the issues selected as priorities and then votes on the order of the priorities.

After the Board determines the priorities for that year, the National Action Network is notified and a link to the priorities is put on the website. NBCC staff then develops background material to explain each priority.

Chris Norton with her son and grandchildren.

For me, the truly fun part of working with the priorities begins when NBCC sends an alert asking the grassroots to contact their Senators and Representatives in Washington about a specific legislative priority. I then send emails to the grassroots network in Minnesota and ask people to email or call their Representative or both Senators to request their support of the legislation.

Securing the support of a Representative or Senator is gratifying. But the best feeling is learning that the legislative priority that thousands from across the country worked to achieve has passed the House and the Senate.

Chris Norton, President of the Minnesota Breast Cancer Coalition, has been a member of NBCC since the 1991 “Do the Write Thing” campaign. She has served on NBCC’s Board of Directors since 2000. Chris is a 22-year breast cancer survivor.

In this mini-symposium at the San Antonio Breast Cancer Symposium (SABCS) in December, three speakers addressed different aspects of the apparently increased risk of developing breast cancer that is associated with high breast tissue density, and also the clinical implications of this association.

Celine Vachon of the Mayo Clinic in Rochester first spoke of the genetics and epidemiology of breast tissue density. She observed that increased density was common, with 16-32% of women in general having more than 50% dense breast tissue, and that these women have a 3-5 fold increased risk of developing breast cancer compared to those with low or no breast density. Among women with breast cancer, up to one third are found in women with a density of over 50%.

Breast density decreases with age, with the greatest decline seen between ages 45-55. But Dr. Vachon also noted the protective value of fatty breast tissue in pre-menopausal women: the higher the amount of fatty breast tissue present in this group of women, the lower the overall density and risk of developing breast cancer.

As to why some women have more dense tissue that others, factors that seemed to be associated with higher density included pre-menopausal status, nulliparity, post-menopausal hormone use and alcohol intake. But Dr. Vachon pointed out that taken together, epidemiological risk factors account for only 20-30% of the variation in breast density in the general population. Genetics appeared to account for a higher percentage of the variance, with 30-60% of the variance attributed to inherited factors.

Norman Boyd of the Ontario Cancer Institute then looked at some of the clinical implications of the observed increased risk associated with high breast density.

With regard to breast cancer characteristics and clinical outcomes, he observed that those with 75% breast density had a 5-fold difference in risk compared to those with less than 10% density, and that extensive density was associated with an overall increased risk of developing both ER+ and ER- tumours, and of all “non-obligate” precursors of invasive tumours such as DCIS and ADH. It was also associated with larger tumours and higher histological grade. However, the risk from death did not appear to be increased.

The implications for screeningwere clear in that mammography is less effective for women with dense breast tissue, who would benefit from alternative screening modalities such as MRI or US. Conversely, women with translucent breast tissue were at lower risk and could therefore consider less frequent screening than is currently standard.

Dr. Boyd also addressed the issue of breast cancer prevention trials and pointed out that unlike most other risk factors for breast cancer, breast density can be changed. He suggested that breast density could be used as a surrogate marker for risk in such trials, which would allow the identification of a group at very high risk of developing breast cancer who might benefit from e.g., tamoxifen therapy, which is known to reduce breast tissue density. But validating breast density as a surrogate marker for risk would take time.

Overall, Dr. Boyd also reminded us that correlation does not prove causation: the apparent higher risk conferred on women with dense breast tissue could simply be down to chance, and the fact that these cancers are often found at a later stage compared to screen-detected tumours.

In the final presentation of the mini-symposium, Thea Tlsty of the University of California, San Francisco looked at the biological basis of breast density and cancer risk. She and her team had examined specifically the relationship between a higher amount of fatty tissue in the breast and lower breast density – also mentioned by Dr. Vachon in her presentation – and had identified a protein, CD36, which appears to modulate fatty tissue in the breast.

Dr. Tlsty and her team carried out both in vitro and in vivo (mouse model) experiments, which appear to show that CD36 protein levels are repressed in all stromal cells within tumour tissues compared to normal adjacent tissue, and that much higher levels of CD36 are found in normal breast tissue overall. So, measuring CD36 levels and finding a way of increasing them as necessary to produce a higher level of fatty breast tissue, could lead potentially to a reduction in the risk of developing breast cancer.

My view

With reference to NBCC’s goals to end breast cancer by January 1, 2020 (Breast Cancer Deadline 2020®), any practical clinical application of Dr. Tlsty’s research seems unlikely to be ready by 2020. In the case of the overall increased risk that is associated with high density breast tissue, as discussed in this mini-symposium, even it could be proved beyond reasonable doubt that there is, in fact, a causal relationship between two, breast density is probably just one part of the jigsaw in any case.

Overall though, in looking at biological aspects of breast cancer risk, I think that Dr. Tlsty and her team’s work seems particularly promising, in that by arriving at a clearer understanding of the biology of breast cancer and the environment in which it develops, new approaches to prevention and intervention may be identified – all of which speaks to the deadline goals, even if not the timing.

I attended the Collaborative Summit on Breast Cancer Research in Washington D.C., held January 31- February 1. The goal of the Summit was to gather researchers, funders, advocates, and industry representatives together to assess the breast cancer research landscape and to develop collaborative projects for moving forward. Below are the remarks I gave during the opening plenary panel on the breast cancer research landscape and on NBCC’s current projects and priorities.

Laura Nikolaides, NBCC Research & Quality Care Program Director

I am excited to be here and to have the chance to talk about the bigger picture of breast cancer research, where we have been and where we should be going. So much of the year is spent down in the weeds when it comes to breast cancer research, when we attend the ASCO meeting or SABCS, or when we review grant proposals, so it is gratifying to have this opportunity to for all of us to pull our heads up from the weeds and to discuss the long view.

And for me, the long view, means thinking about my 13-year-old daughter. Where do we need to be by the time she and her friends are adults? Are we on track? Will things be dramatically different in ten, twenty, thirty years when it comes to breast cancer? Or will mothers, grandmothers and young women and even men still be dying of breast cancer? Will we know by then why breast cancer cells can lay dormant for 15 years to reemerge and metastasize? Will we know how to eliminate those dormant cells from the beginning? And what about women who have aggressive disease from the get-go. Will we understand why it developed and more importantly know how to stop the progression for the long-term?

Unfortunately, I don’t see dramatic change on the horizon with current approaches. The ACS predicts that over 300,000 women will be diagnosed this year with in situ or invasive breast cancer. Dr. Gil Welch and others predict that between 30 to 50% of those could be considered overdiagnosis. We continue to add more women into the equation, putting them at risk of harm from treatments, and yet, are we seeing a difference in the measures that matter? Yes, we have seen steady, incremental declines in breast cancer mortality since the early 90s, but there has been no acceleration in this decline. And do we know what this really means? What IS working for women and what is not? Do we know how many women have died from the treatments? Do we know if death from breast cancer is being delayed rather than prevented? Are we really any closer to knowing how to prevent breast cancer or a breast cancer death for an individual woman?

What we do know is that the rate of diagnoses of Stage IV disease has remained constant for 30 years. What we do know is that 40,000 women and men will die from the disease again this year. What we do know is that the median survival for metastatic breast cancer has remained constant, at about three years.

With billions in resources and decades of effort, we see discovery of new targets, and development of new agents, that extend life by three to four months at a time, if we are lucky. We are learning a lot about the DNA of breast tumors, and the layers of complexity involved, but are we really gaining a better understanding of the why and how of breast cancer? The kind of understanding that will allow for development of gamechangers?

A pharma analysis report prepared a few years ago concluded that with what is currently in the pipeline, and based on historical trends, the median survival for metastatic breast cancer will inch forward from three years, to three years and six months by the year 2021. Important progress and critical efforts, yes, but is it good enough? No, it is not good enough. We can and must do better. We need new approaches to complement the old ones. We need new ways to look at the disease. We need to find approaches that give us hope of doing better. Targeting of mutations alone, in a disease that constantly grows and mutates, will never be enough.

In 2010, NBCC set a deadline. By the end of the decade we need to understand much more about metastasis and about development of primary breast cancer, so that we can prevent deaths and end this disease. The deadline is a tool to cause disruptive change. The purpose is to shift the focus, to look at the disease differently, to consider new approaches that give us hope of doing better.

How do we get there? To achieve success we have to do more than bring everyone together who works in the field, increase funding, and see what happens. We need to demand more focused research with the end results in mind. We need to bring new perspectives to the table. We need more translational research. And we need to measure what matters. It may just take having specific goals in mind, timelines, and yes, deadlines to get us there.

Many say to us, that’s not how science works. But, I know how science works. I did graduate work in nutritional biochemistry at Cornell University, I carried out a large thesis project involving lactating rats, looking at the impact of malnutrition on milk composition. I know that science works by asking questions, and figuring out how to test theories about the answers to those questions.

So what if we can all agree on what those questions should be? Questions that will help drive us to an understanding of how to prevent deaths from breast cancer? Science can work towards meeting goals and yes – even meeting deadlines. I know I had to answer my research questions in a certain time to finish my thesis and graduate. Scientists meet deadlines all the time. Right now, in the field of breast cancer research, we have many people asking many questions in an infinite number of directions. We are producing incredible volumes of information. But for all of that effort we are seeing minimal benefit for women. Something has to change. We need leadership and coordination of efforts, sharing of information, all of us working together on common goals. We need the will to ask the right questions, and the resources to explore those questions. And then we have to measure what matters to judge success.

NBCC has spent the last two years exploring how to do this on a small scale with what we call Artemis Projects. These are a series of collaborations among patient advocates and researchers from diverse perspectives. The purpose of the collaborations is to develop strategies, research plans and timelines for answering key breast cancer questions. Patient advocates are there to make sure efforts are always focused on the end result.

The first of our Artemis Projects was launched in 2011, bringing together a group of advocates and scientists to take a strategic, systematic yet broad approach to the development of a breast cancer preventive vaccine within five years. We bring together a group of close to 40 each year to assess progress and to readjust plans. We also hold smaller meetings to bring together experts to bear on particular issues as needed, and have an online community for the project to keep things moving in between meetings.

As most of you know, we don’t typically fund research directly. But through the generous support of National Philanthropic Trust (NPT), NBCC has awarded two seed grants as part of this project, one to Dr. Paul Spellman and Dr. Joe Gray of Oregon Health and Science University to identify possible vaccine targets using existing and developing human genomic data within different breast cancer subtypes. And a second seed grant was awarded to Dr. Paul Ewald at the University of Louisville, and Dr. Vladimir Belyi of The Cancer Institute of NJ to look at infectious agents and breast cancer. Bioinformatic tools will be used to take a systematic approach to intersect the genomes of known viruses and a broad array of cellular pathogens to identify their presence and prevalence in breast cancer genomes relative to normal breast tissue. Initial data from both of these seed grants will be presented at the next annual meeting in March.

We will also be kicking off a second Artemis Project on Metastasis in June to focus on tumor dormancy. As with the Artemis Project on the Preventive Vaccine, our goal is to bring together investigators with diverse perspectives to brainstorm and develop innovative strategies for accelerating progress.

In summary, I think we do have the will and the resources to come together on asking the right questions. We have heard from others this morning about new initiatives focused on prevention and metastasis. I see positive steps being taken to prove that pharma analysis wrong. If we can keep the end result in mind, where we want to be when all of those 13 year olds are 21 year old adults and beyond, I feel hopeful we can change the course. I look forward to the rest of the meeting for further discussion on how we are going to get there. Thank-you.

NBCC's study group at SABCS. NBCC Advocate Nancy Ryan is pictured in yellow.

NBCC asked a group of gifted and seasoned advocates who attended the San Antonio Breast Cancer Symposium to develop critical pieces on sessions that related to the two areas of focus for Breast Cancer Deadline 2020®. The areas are primary prevention of breast cancer and understanding metastasis and preventing deaths from the disease. Watch for a series of these excellent articles which include assessments of the relevance of the research to Breast Cancer Deadline 2020® goals, on the NBCC blog in the coming weeks. NBCC advocate, Nancy Ryan, starts off the series with a review of a poster presentation on Metformin and Statins.

Poster Summary
Poster Discussion 3 focused on two agents: the drug metformin, an insulin lowering agent used in the treatment of diabetes, and statins, a class of drugs used primarily to treat lipid disorders, commonly used to lower cholesterol.

Metformin
Based on observational studies suggesting metformin use in diabetic patients reduces the risk of certain cancers, several clinical trials presented in this session explored possible mechanisms for a metformin effect in patients with breast cancer.

Italian researchers measured cancer cell apoptosis (cell death) in 897 patients who were randomized to take metformin or a placebo for four weeks before surgery. (This kind of study is called a “window of opportunity trial”—a very short course of targeted therapy, placebo or no drug is given prior to surgery.) Apoptosis was measured in biopsy samples before starting metformin or placebo and again prior to surgery. The levels of apoptosis as measured by an assay called TUNEL (terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling) were higher in the surgical specimens than in the baseline biopsies, but the difference between the two arms was not significant. However, there was a borderline significant trend to a different metformin effect according to whether women were or were not insulin resistant. Insulin resistance is the body’s decreased ability to respond to the hormone insulin, which helps the body manage sugar. Patients who were not insulin resistant had a higher TUNEL level (higher apoptosis) with metformin than women with insulin resistance with metformin.

Following a different track, Canadian researchers further analyzed cancer tissues from a pre-operative window of opportunity trial to evaluate Adenosine Monophosphate Protein Kinase (AMPK). Protein kinases help regulate cell function. AMPK helps to maintain cellular energy homeostatsis. In this study, 47 non-diabetic patients were randomized to receive metformin or no drug before surgery. All had core biopsies at diagnosis and before surgery. Significant up-regulation, or increase in expression, of pAMPK and a fall in a protein associated with cell proliferation (Ki67) were demonstrated in treated patients compared to the control group. The investigators concluded, “Since down-regulation of pAMPK is a feature of breast cancer, this suggests mechanistic evidence for the therapeutic effects of metformin.”

Another small pre-surgical study enrolled 35 overweight and obese women. They started metformin two to four weeks before surgery. The primary endpoint was to analyze the change in Ki67 activities from baseline to surgery. Researchers “Did not identify a significant difference in tumor proliferation as measured by In (ki-67) tumor levels, before and after metformin use.”

Yet another group, looking at 39 non-diabetic patients given metformin from core biopsy to surgery reported, “Ki67 staining in tumor tissue decreased significantly and TUNEL increased significantly.” In other words, the measure of tumor cell proliferation decreased and the measure of apoptosis (cell death) increased.

Statins
Several posters dealt with the relationship between statins and breast cancer. Previous studies of the role of statins in breast cancer offer conflicting results. Some show no effect on cancer incidence, others show a small decrease in risk. Researchers are interested in the anti-tumor and anti-inflammatory properties of statins. Hence, some work has focused on Inflammatory Breast Cancer (IBC), a rare and aggressive form of breast cancer.

One team reviewed outcomes in 724 patients being treated for primary IBC over a 16-year period (a retrospective cohort study). They compared patients who were taking statins at the time of their IBC diagnosis and those who were not. Median PFS (progression free survival) was 1.76 years in patients with no record of statin use compared to 2.47 years in patients who reported using lipophilic (fat-soluble) statins, and 4.88 years in patients with a history of hydrophilic (water soluble) statin use. Researchers were surprised that the type of statin made a difference. The overall survival endpoint did not reach significance. The team concluded, “A prospective randomized study to evaluate the potential survival benefits of statins in the IBC population is warranted.” In other words, more work needs to be done.

In a Swedish window of opportunity trial researchers investigated the “anti-proliferative impact of a two-week, high-dose lipophilic statin therapy in patients with primary invasive breast cancer, while addressing the potential of HMGCR as a prognostic and potential predictive marker.” HMGCR (3-hydroxy-3-methylglutaryl-Coenzyme A reductase) is an enzyme involved in cholesterol synthesis. Previous studies have shown an HMCGR variation protein expression in human breast cancer. Atorvastin-induced tumor response was measured by Ki67. Atorvastin is commonly known as Lipitor. According to the analysis, “Among all tumors, Ki67-index in core biopsies showed an average of 24.0% compared to surgical samples with an average index of 21.9%, providing an average absolute reduction of 2.1% and an average relative reduction of 7.6%. The study also showed upregulation (increase in expression) of HMGCR in samples following two weeks of atorvastatin treatment and indicated that HMGCR is targeted by statins and could serve as a predictive marker for selecting who would benefit from treatment.

In updated findings from the Women’s Health Initiative (WHI), another team concluded, “There was no association between prior use of statins and risk of invasive breast cancer in the WHI.” The population studied included over 150,000 women enrolled in three clinical trials and one observational study. This result was a disappointing follow-up to a previous WHI analysis of 4,383 cases that showed an 18% reduction in breast cancer risk for users of lipophilic (fat soluble) statins (although no overall reduction in breast cancer risk).

Panel DiscussionThe panel discussion following poster viewing raised numerous questions. Dr. Michael Pollak noted that most lab models use much higher doses of metformin than conventional human doses. Window of opportunity studies, he said, can be difficult to interpret because of small sample size, confounding factors and shortness of duration. He argued that these studies have not strengthened the evidence for metformin use in breast cancer. Other issues of concern involve potential flaws in tissue sampling when comparing core biopsy material to surgical samples, and whether metformin would be more useful as prevention or treatment. Also, current anti-diabetic doses of metformin are relatively safe, but are they large enough to affect breast cancer? A current Canadian NCIC Clinical Trials Group Phase III clinical trial (MA32) is underway to compare invasive disease-free survival of patients with early-stage breast cancer treated with metformin vs. placebo in addition to standard adjuvant therapy. Results are not expected for three years.

Dr. Vered Stearns noted that a meta-analysis of statin use and breast cancer showed no benefit in reducing risk. He cited several limitations of the posters presented. For example, statin users may also take other types of drugs not accounted for, there are many different types of statins in use, and we do not have the necessary biomarkers to measure the effects of statins.

The “take home message” from the panelists was clear — further research is warranted. We still need large, collaborative, well-run prospective studies on the role of both metformin and statins in reducing risk for and treating breast cancer.

Advocate Analysis
It would be great if there was a drug that prevented breast cancer, recurrence or breast cancer metastasis — one that is well tolerated, already in wide use, easy to administer and relatively inexpensive. With a drug like metformin or statins — drugs that could be “repurposed” from treating one disease to treating another — we’d be closer to reaching our Breast Cancer Deadline 2020®January 1, 2020 goal.

Unfortunately, based on this poster discussion, we are still a long way away from that goal with metformin or statins. The relationship between insulin, obesity, diabetes, inflammation, metformin and statins is complex and not clear. It is similar to a 1,000 tiny-piece jig-saw puzzle in the toy store window. Researchers have only just completed the border. The complicated internal connections have yet to be deciphered.

It was not clear to what extent advocates were involved in any of the posters presented in this session. The women who consented to participating in the window of opportunity clinical trials are to be commended. The multi-centered MA32 clinical trial is currently enrolling patients and has trial sites in many US states, Canada, Switzerland, and the UK. Advocates can help by getting the word out about this trial.

In summary, I found the poster study questions intriguing because I felt like I was watching the science train switching tracks from basic observational studies to lab and clinical work designed to ferret out the “why” and “how” of the observations. I am excited about the idea of using an existing drug to end breast cancer, but if metformin or statins are going to help us reach our Breast Cancer Deadline 2020® goal, the train needs to get up a real head of steam, and soon. You might say we need a Shinkansen (Japan’s high-speed “Bullet Train”) for this task. The MA32 clinical trial may answer some of the questions raised during this session and help accelerate the train. Whether the train arrives at the station by January 1, 2020, remains to be seen.

After attending my fifth San Antonio Breast Cancer Symposium it seems, once again, that we are inching forward ever so slowly in improving survival for some women, but at a great cost to many. Much effort is going towards breast cancer research, but these efforts seem diffuse, with a hit or miss strategy. Many results never reach the clinic. Those that do may or may not lead to marginal improvements for some, but most often add risk of toxicities for many. Thousands of researchers and oncologists once again gathered to hear about studies focused on comparing different doses, different schedules, different combinations of treatments, with some showing marginal improvements in survival, most showing no difference. Very few presentations focused on how to reduce the risk of toxicities from treatment for the increasing numbers of women being diagnosed with early breast cancer, many of whom may have been fine with no treatment at all. Almost no presentations focused on preventing the disease in the first place.

I like to imagine how different it could be if there was a mission-driven approach to breast cancer research, and everyone was coming together to strategize about achieving very specific goals, rather than diffuse pursuits in many directions. What if there was a coordinated effort throughout the year to answer a few directed questions that could lead to understanding how to prevent deaths from the disease? How exciting it would be to come together each year to hear about that kind of progress.

Instead, the presentations I heard often seemed driven by the needs of pharma or business, but not women. How can we recapture the market for a drug going off patent? Or how do we move the drug to another stage of the disease and capture a new market? Or the needs of scientists. Many presentations this year looked at associations between genomic profiles and various factors of the disease or treatments. This is elegant science, which leads to papers and new lines of laboratory research for next year, but I didn’t hear much evidence that this work was leading to benefits for women.

A few presenters said we may be going about it all wrong. Dr. Fatima Cardoso, in a presentation on treatment guidelines for women with metastatic breast cancer, said we need to think of metastatic disease as a different disease and study it as a different disease, not as grounds for studying adjuvant treatment of early breast cancer. The current model is to develop a drug that shrinks tumors, prove its efficacy in the metastatic setting, and then move it into the adjuvant setting to prevent recurrences. And add it on to existing standard of care to see if it improves survival. The problem, said Dr. George Sledge in a presentation on tumor dormancy, is that agents that can halt progression in a metastatic setting may be completely different from those that can remove residual disease after surgery for early breast cancer, or that maintain tumor dormancy and prevent a reemergence of the disease. I would also say that another problem of this add-on approach to breast cancer treatment is that while sometimes bringing marginal benefit, this approach continues to escalate the risk of treatment toxicities.

Our work must continue as advocates for women, to right this ship, getting researchers to focus on the appropriate questions that will lead to meaningful progress and lower toxicities. This year, we remain hopeful that a new class of drugs, antibody-drug conjugates (ADCs), will alter cancer care, bringing greater efficacy and at the same time greatly reducing the harms of treatment. These ADCs can deliver chemotherapy directly to cancer cells, resulting in cell death, while avoiding harm to normal cells. But they must be evaluated on their own, and not simply added to regimens of systemic chemotherapy. We continue to advocate for the company (Genentech), that developed an ADC for HER2+ breast cancer called T-DM1, to evaluate the new drug in early breast cancer without systemic chemotherapy, to finally give the promise of targeted breast cancer treatment, with lower toxicity, a chance to be achieved.

Specific findings reported at this year’s symposium:

CDK-inhibitor
This was one bright spot at the meeting. Encouraging results were presented from a small study of a new agent, done in two parts, with just under 200 women who had ER+ advanced breast cancer. The agent, which is identified as PD 0332991, was developed from the work of Dr. Dennis Slamon and colleagues, funded by a DOD Innovator Award. It is an inhibitor of cyclin-dependent kinases (CDK), necessary for DNA synthesis. In the first part of the study, women were randomized to receive PD 0332991 with letrozole, or to receive letrozole alone. In the second part of the study women were screened for a biomarker, abnormal levels of the CDK protein. The good news is that women who took the CDK inhibitor had a median progression free survival of 26.1 months, compared to 7.5 months for the women who took letrozole alone. The disappointing news was that the effort to identify a biomarker of response beyond ER was not successful. More low white and red blood cell counts were reported with the new drug, but were readily managed and produced few complications for the women. A phase III trial of the CDK inhibitor begins in 2013.

Avastin
Though FDA approval for Avastin in the metastatic breast cancer setting was revoked last year, clinical trials of the drug are continuing, and we continue to get reports. I wonder how many women are still receiving this drug and what it would take for researchers to stop these trials. Two studies were presented this year – the BEATRICE trial, looking at Avastin to prevent recurrence in women with triple negative disease, and the LEA trial, looking at Avastin in combination with hormonal treatment for first line treatment of metastatic breast cancer. In BEATRICE, a trial of over 2500 patients, the three year recurrence rate was virtually the same for both arms of the study, with greater toxicity in the Avastin arm. In LEA, investigators were hoping to show that Avastin if given without chemotherapy, would be more beneficial. But results from the trial of 380 women showed no differences in overall survival, and in fact, there was a trend toward lower survival in the Avastin arm, though this wasn’t statistically significant.

Eribulin
Results were reported from a phase III trial of eribulin mesylate for women with previously treated metastatic breast cancer, showing no significant improvement in overall survival, when compared to capecitabine.

Letrozole for Lobular Carcinoma
Lobular carcinoma accounts for approximately 10% of invasive breast cancer, and is usually ER+. An analysis from BIG I-98, a study comparing letrozole with tamoxifen for preventing recurrences in post-menopausal women, was presented showing that women with lobular cancers were deriving greater benefit from letrozole, than women with invasive ductal carcinoma. Previous results had failed to demonstrate an overall survival advantage with letrozole for all of the women in the study, but this subset analysis did find a greater overall survival advantage with letrozole vs. tamoxifen for women with invasive lobular carcinoma.

Faslodex
Results from CONFIRM, a study of different doses of Faslodex for recurrent or metastatic breast cancer, were presented showing a median overall survival of 26.4 months for the higher 500 mg dose of Faslodex compared to 22.3 months for the smaller dose of 250mg. At least one serious adverse event was experienced by 8.9% of the women receiving the higher dose, compared to 6.7% receiving the lower dose.

Dose Dense Chemotherapy
A ten-year follow-up analysis of adjuvant dose dense chemotherapy, given every two weeks and at a higher dose, instead of the standard dose every three weeks, showed a benefit in overall survival. In this study of over 1200 women with 4 or more positive lymph nodes, 10 year OS rates were 69% for those on the dose dense regimen, compared with 59% for those receiving the standard regimen. Nine cases of leukemia were reported in the dose dense arm vs. two in the standard arm.

Leukemia risk from treatment for early breast cancer
From clinical trials results we know that adjuvant treatment for breast cancer increases the risk of developing leukemia. A review of the records from over 20,000 women treated for early breast cancer found an overall cumulative risk of developing leukemia after ten years of 0.27%. The women who developed leukemia tended to be older, and the risk increased in those receiving chemotherapy vs. no chemotherapy, and for any radiotherapy vs no radiotherapy. No increased risk was observed if a taxane was added to an anthracylcine chemotherapy regimen.

Herceptin
Results were presented at this symposium and earlier this year at a European meeting on the optimal duration of Herceptin treatment for HER+ early breast cancer. The HERA trial found no difference in recurrence or survival between one or two years of treatment, and the PHARE trial, which was designed to determine if six months did not give a worse outcome, had results that were inconclusive. One year of Herceptin treatment remains the standard of care.

Tamoxifen
The ATLAS study (Adjuvant Tamoxifen – Longer Against Shorter) was the one most covered by the media this year. In this study, over 6800 women who had completed five years of treatment with tamoxifen for early breast cancer were randomized to continue tamoxifen for five more years or to stop treatment. It’s worth noting that there was not a placebo for the group who stopped treatment, weakening the design of the study. Compliance was approximately 80% and a benefit was found for the longer treatment, but it didn’t show up until after it was completed, in years 10-15 following diagnosis. The benefit was modest and the risk of side effects did increase. Breast cancer mortality was 15% for those women who stopped tamoxifen at five years, compared to 12.2% for those who continued for ten years. The cumulative risk of recurrence was 21.4% for women who took tamoxifen for ten years, compared to 25.1% for those who stopped. The rate of endometrial cancer was 3.1% in the ten year group, compared with 1.6% in the group that stopped at five. There was also an increased risk of pulmonary embolism in the ten year treatment group, though there were no differences in the risk of stroke.

Radiation Therapy
Several studies on radiotherapy were presented. Most notably, ten year follow-up from the START trial demonstrated that three weeks of treatment is at least as safe and effective as the standard five-week schedule of treatments. Researchers with the TARGIT-A trial, looking at a single dose of radiation delivered internally vs. whole breast externally delivered radiation, presented preliminary results showing no differences in breast cancer deaths but a decreased mortality with the single dose from cardiac related deaths and second cancers.

]]>http://blog.breastcancerdeadline2020.org/?feed=rss2&p=4722Mammography In the News …Againhttp://blog.breastcancerdeadline2020.org/?p=465
http://blog.breastcancerdeadline2020.org/?p=465#commentsThu, 29 Nov 2012 18:23:38 +0000BreastCancerDeadline2020http://blog.breastcancerdeadline2020.org/?p=465Continue reading →]]>NBCC has taken the position for many years that the benefits of screening mammography in reducing mortality are modest and that there are harms associated with screening, based on randomized clinical trial data. No individual woman can be assured that screening mammography will be effective for her, and from a public health perspective, the harms and public health costs of screening mammography may outweigh the modest benefits of the intervention. Last week, Dr. H. Gilbert Welch and Dr.Archie Bleyer published a study looking at over three decades of data, providing strong observational evidence that this is indeed the case.

The study, published in the NEJM, looked at the impact of mammography screening on breast-cancer incidence between 1976 and 2008 in US women over 40. The authors examined the change in incidence of early-stage and late-stage breast cancer after the introduction of wide-spread screening in the mid-1980s. They found that while the incidence of early-stage (DCIS and breast cancer localized to the breast only) increased significantly, the incidence of late-stage (regional and metastatic breast cancer) decreased only slightly.

The incidence of metastatic breast cancer, the number we most need to change with screening, had not changed at all over the three decades. Dr. Welch and Dr. Bleyer estimate that over one million women have been over-diagnosed as a result of mammography screening, and have undergone treatments involving surgery, radiation, hormones, and chemotherapy for abnormalities that otherwise would not have caused illness. Dr. Welch explains the study and results in a brief YouTube presentation for advocates and the public. Watch it here.

Following publication of the study, Dr. David Newman wrote in the NYTimesWell blog, “It is affirming to see this newest study. But it raises an awkward question: why would a major medical journal publish an observational study about the effects of screening mammography years after randomized trials have answered the question? Perhaps it is because many doctors and patients continue to ignore the science on mammograms.”

It’s hard to blame the patients when the media messages are so mixed. Following directly on the heels of the NEJM study, were reports from the annual radiologists’ meeting expressing concern about decreased screening and possible “missed cancers.” They don’t acknowledge the results of randomized clinical trials and observational data showing that finding cancers and DCIS through mammography isn’t translating into significantly fewer deaths, while at the same time is causing many women to undergo treatments they would have been fine without.

NBCC continues to believe that a woman’s decision to undergo a screening mammogram must be made on an individual level, based on quality information about her specific risk factors, and her personal preferences. Women who have symptoms of breast cancer such as a lump, pain or nipple discharge should seek a diagnostic mammogram. We can only hope that the latest NEJM study will help put the issue to rest and we can move on. Ultimately, resources must be devoted to finding effective preventions and treatments for breast cancer and tools that detect breast cancer truly early.

Do you remember the day of breast cancer diagnosis? I do….the shock, the fear, the unknown. At first the tasks of survivorship appeared physical, focused on the body. But once these choices were in place, I was swept into post-treatment, a psychologically challenging time. As a psychotherapist, I offer you one perspective on moving from cancer to advocacy, with a nod to the complexity of the process. Personally, it took a one-on-one introduction to NBCC, through my daughter Giselle, to pull me into both advocacy and a further step toward my own continued psychological growth.

The First Role of Someone Diagnosed with Breast Cancer Is to Survive

Both during and after whatever treatment is chosen, we deal with very basic psychological tasks. One major task is trust. And just as the infant learns trust from predictable, kind, nurturing parents, we have to again re-form our trust networks. We now include medical facilities and personnel, family and friends, colleagues, religious affiliations, neighbors, peer groups who have been supportive and understanding. Sometimes the psychological work includes reworking a relationship that no longer feels trustworthy at this point, or letting it go. Grief becomes a partner for each of us. It’s during this stage that survivors often group into local self-help organizations, as they need to be with others who understand and are trustworthy. I found several excellent local groups, in particular CRAAB! But at that stage in my own journey, I was most comfortable leaning into the support primarily from my friends and family.

The Second Role Is to Redefine Life

After diagnosis and treatment for breast cancer our bodies are not the same—we are not the same. This is a critical stage in the psychological recovery and growth of the breast cancer advocate. There is no timeline for this stage; some enter immediately, during or after first treatment, but many take a year or two to move past survival into “redefinition.” It took me longer, as I continued in my practice through treatment and for nearly two years following. Although I still treasure being a part of the Albany Medical College Department of Psychiatry, and value my continued work with my peer supervision group, only when I closed the practice could I gather momentum to move in new directions. This was a difficult decision, but right for me.

Moving past any shame or doubt that accompany cancer, beginning to develop pride and determination, beginning to make active choices in all aspects of life, the “redefine” has an unparalleled opportunity to re-examine values and roles in life. Work may no longer fit needs, or need to be restructured. Relationships are re-examined. This is the stage at which the survivor begins to look outside of herself/himself and can choose to initiate change on a larger scale. Some advocates never move past the immediate redefinition from patient to survivor but many, certainly those reading this blog, shift into advocacy. I closed my practice and had new business cards made, highlighting growing aspects of my own identity—artist and advocate! NBCC has been a leading organization to gather these new advocates and train them to speak the languages they need to move into the third role.

Psychologically, the Third Role Is to Act on Redefinition and Continue to Change as the Opportunities Arise

With the scientific education, political focus, and an action support net cast around the world, NBCC enables cancer survivors to act. Educating ourselves, working for the health of others, gathering smaller organizations in coalition, and always aware of that small step into metastasis, we network with others who act.

It was at this point that I began to accept tasks that would have previously been unimaginable. Currently, among other responsibilities, I am serving a second term on the New York State Health Research Science Board; I am a member of the Scientific Advisory Committee of the Love/Avon Army of Women; I have been a consumer reviewer for the DOD Breast Cancer Research Program; and I serve as a reviewer of breast cancer-related medical journalism for Gary Schwitzer’s “healthnewsreview.org.” Combining life as a painter, an advocate, friend and family member, I have experienced a richness that at times leaves me breathless. It balances the fear and anxiety that will always remain.

It takes courage to continue growing as an advocate, to try the new, to meet or develop a needed area of advocacy, to walk through that open door or pound on the closed. Those of us who have survived breast cancer will only continue to grow psychologically if we both allow intimacy with other survivors (all those hugs count!) and find ways to protect those who have not suffered this illness. We can step into a life of a larger creativity and integrity, and impact the social, scientific, and political environment that holds us all. We are, after all, our sisters’ and brothers’ keepers.

In September 2010, the National Breast Cancer Coalition (NBCC) launched Breast Cancer Deadline 2020®, an unprecedented, bold initiative backed by a comprehensive strategy to end breast cancer by January 1, 2020. One component of Breast Cancer Deadline 2020® is a grassroots campaign to collect more than 290,000 signatures on a petition calling on the next President to support Breast Cancer Deadline 2020®.

Why call on the president? The answer is simple.

The President can create a vision, set a goal and galvanize a nation. It took enormous courage for President John F. Kennedy to announce in 1961 his goal of sending a man to the moon within a decade. But the time was right. The United States faced a challenge in the arena of space exploration. The President knew the country was positioned to become a world leader in this arena. He knew our country had the talent and the potential technology to accomplish the task.

Several decades of breast cancer research have brought our nation to a similar juncture. Despite billions of dollars invested in research, awareness, screening and treatment, breast cancer incidence has increased and breast cancer mortality has not declined commensurate with our investment. This year alone, more than 290,000 American women and men will be diagnosed with breast cancer. What we do have are the tools and talent to turn these statistics around. We have gained unprecedented insights into the genetics and biology of breast cancer. We have sophisticated technology to analyze, store and manipulate enormous amounts of data about cancer. We have dedicated researchers who understand the devastating emotional, financial and personal burden shouldered by breast cancer patients, their families, friends and caregivers.

What we need is new approach, a new vision and a new “call to action.” The President can provide that leadership. The President has far-reaching opportunities to bring national attention to ending this disease. Presidential leadership can inspire every stakeholder— researchers, trained advocates, doctors, nurses, students, legislators, policy makers—to harness the knowledge we have gained over the past several decades and focus it on saving lives. The President can use the power of his office to inspire innovation and creativity in the scientific community. The President can help to leverage our current research investment by encouraging bold, new avenues of research designed to investigate breast cancer prevention and preventing metastasis. The President can support those who work within federal agencies that conduct breast cancer research, carry out health care policy, and manage national cancer prevention, screening and control programs. And finally, the President can announce his support for Breast Cancer Deadline 2020®.

Everyone has a role to play in ending breast cancer, including a President with the courage, vision and leadership to accomplish the task.